EXECUTIVE SUMMARY

A Phase III study will determine whether a long-acting form of the anti-HIV drug, cabotegravir, injected once every eight weeks, can safely protect people from HIV infection at least as well as Truvada, a combination of anti-HIV medications taken daily as an oral tablet.

  • If found to be safe and effective for HIV pre-exposure prophylaxis, injectable cabotegravir may be easier for some people to adhere to than daily oral Truvada.
  • The study will enroll 4,500 men who have sex with men and transgender women who have sex with men, all 18 years or older and at high risk for HIV infection, at 45 clinical sites.

The first large-scale clinical trial of a long-acting injectable drug for HIV prevention has just been launched. The Phase III study, which will enroll participants at 45 sites in Argentina, Brazil, India, Peru, South Africa, Thailand, the United States, and Vietnam, will examine whether a long-acting form of the anti-HIV drug, cabotegravir, injected once every eight weeks, can safely protect people from HIV infection at least as well as a combination of anti-HIV medications taken daily as an oral tablet. Truvada, which consists of the anti-HIV drugs emtricitabine and tenofovir disoproxil fumarate, is the only medication currently approved for HIV pre-exposure prophylaxis (PrEP).

The HIV Prevention Trials Network has launched the HPTN 083 study to evaluate whether injectable cabotegravir can safely protect men who have sex with men and transgender women who have sex with men from acquiring HIV as well as daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). If found to be safe and effective for HIV PrEP, injectable cabotegravir may be easier for some people to adhere to than daily oral TDF/FTC.

The study’s creators will enroll 4,500 men who have sex with men and transgender women who have sex with men, all 18 years or older and at high risk for HIV infection, at 45 clinical sites. Results are expected in 2021.

The annual number of new HIV infections among young people, especially young men who have sex with men and transgender women who have sex with men, has been on the rise despite nearly flat HIV incidence among adults worldwide, noted Raphael Landovitz, MD, MSc, HPTN 083 protocol chair, in a statement regarding the trial enrollment.

“It is essential to develop multiple effective HIV prevention modalities so the most vulnerable populations have a choice of preventive options,” said Landovitz, who serves as an associate professor of medicine at the David Geffen School of Medicine at UCLA, and associate director of the UCLA Center for Clinical AIDS Research & Education. “We hope injectable cabotegravir will become one such modality.”

Researchers will follow participants in the HPTN 083 study for an average of 4.5 years. During their first five weeks after enrollment, study participants will receive two daily oral tablets: either cabotegravir or Truvada, and a placebo pill. Beginning in the sixth week, participants in the cabotegravir group will receive injections of cabotegravir and placebo tablets to be taken orally daily, while participants in the Truvada group will receive placebo injections and daily oral doses of Truvada tablets. Study staff will administer injections. The first two injections will occur four weeks apart, then once every eight weeks for an average of nearly 3.5 years. After completing the injections, all participants will be offered 48 weeks of PrEP with daily oral Truvada.

All study participants will receive HIV prevention counseling, condoms and lubricant, as well as counseling to encourage and support adherence to the daily oral pill. Participants will be tested for sexually transmitted infections (STIs) throughout the study and referred for appropriate treatment if diagnosed with an STI. Study participants who become HIV-infected during the trial will stop receiving the study products and be referred to local medical providers for HIV care and treatment.

“The HPTN 083 study has the potential to provide game-changing data as the first large-scale test of a long-acting injectable drug for HIV prevention,” noted Protocol Co-Chair Beatriz Grinsztejn, MD, PhD, in the enrollment announcement. Grinsztejn directs the Instituto de Pesquisa Clinica Evandro Chagas HIV/AIDS Clinical Research Centre of the Oswaldo Cruz Foundation–Fiocruz in Rio de Janeiro, Brazil.

Separate Study for Use in Women

Injectable cabotegravir also will be tested for HIV prevention in women. The HPTN 084 study will examine the safety and efficacy of injectable cabotegravir in a study that will take place in sub-Saharan Africa. The trial is expected to launch in 2017.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, is sponsoring HPTN 083. The funding for the HIV prevention research uses a new approach: NIAID is co-funding the trial with the pharmaceutical company ViiV Healthcare, while the NIH-funded HIV Prevention Trials Network is conducting the study. Both ViiV Healthcare and Gilead Sciences, Inc., are providing the study medications.

More HIV prevention tools are needed that fit easily into people’s lives, says Anthony Fauci, MD, NIAID director. Taking a daily pill can be difficult for some people, so some individuals may find an every-eight-weeks dosage schedule more convenient. If injectable cabotegravir is found to be effective for PrEP, it may be an easier medication for some people to adhere to than a daily oral pill. Some people also may find periodic injections to be a more discreet form of HIV prevention than daily pills and, thus, may prefer injectable cabotegravir for that reason, public health officials note.

“Although daily oral Truvada clearly works for HIV prevention, taking a daily pill while feeling healthy can be difficult for some people,” Fauci said in a statement. “If proven effective, injectable cabotegravir has the potential to become an acceptable, discreet, and convenient alternative for HIV prevention.”